Watson G Stennis, Craft Suzanne
Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA 98108, USA.
J Neurol Sci. 2006 Jun 15;245(1-2):21-33. doi: 10.1016/j.jns.2005.08.017. Epub 2006 Apr 24.
Insulin resistance (reduced ability of insulin to stimulate glucose utilization) is common in North American and Europe, where as many as one third of all older adults suffer from prodromal or clinical type 2 diabetes mellitus. It has long been known that insulin-resistant conditions adversely affect general health status. A growing body of findings suggests that insulin contributes to normal brain functioning and that peripheral insulin abnormalities increase the risk for memory loss and neurodegenerative disorders such as Alzheimer's disease. Potential mechanisms for these effects include insulin's role in cerebral glucose metabolism, peptide regulation, modulation of neurotransmitter levels, and modulation of many aspects of the inflammatory network. An intriguing question is whether insulin abnormalities also influence the pathophysiology of multiple sclerosis (MS), an autoimmune disorder characterized by elevated inflammatory biomarkers, central nervous system white matter lesions, axonal degeneration, and cognitive impairment. MS increases the risk for type 1 diabetes mellitus. Furthermore, the lack of association between MS and type 2 diabetes may suggest that insulin resistance affects patients with MS and the general population at the same alarming rate. Therefore, insulin resistance may exacerbate phenomena that are common to MS and insulin-resistant conditions, such as cognitive impairments and elevated inflammatory responses. Interestingly, the thiazolidinediones, which are used to treat patients with type 2 diabetes, have been proposed as potential therapeutic agents for both Alzheimer's disease and MS. The agents improve insulin sensitivity, reduce hyperinsulinemia, and exert anti-inflammatory actions. Ongoing studies will determine whether thiazolidinediones improve cognitive functioning for patients with type 2 diabetes or Alzheimer's disease. Future studies are needed to examine the effects of thiazolidinediones on patients with MS.
胰岛素抵抗（胰岛素刺激葡萄糖利用的能力降低）在北美和欧洲很常见，在这些地区，多达三分之一的老年人患有前驱性或临床2型糖尿病。长期以来，人们一直知道胰岛素抵抗状态会对总体健康状况产生不利影响。越来越多的研究结果表明，胰岛素有助于大脑正常运作，而外周胰岛素异常会增加记忆力丧失和神经退行性疾病（如阿尔茨海默病）的风险。这些作用的潜在机制包括胰岛素在脑葡萄糖代谢、肽调节、神经递质水平调节以及炎症网络多个方面的调节中的作用。一个有趣的问题是，胰岛素异常是否也会影响多发性硬化症（MS）的病理生理学，MS是一种自身免疫性疾病，其特征是炎症生物标志物升高、中枢神经系统白质病变、轴突退化和认知障碍。MS会增加1型糖尿病的风险。此外，MS与2型糖尿病之间缺乏关联可能表明，胰岛素抵抗以同样惊人的速度影响着MS患者和普通人群。因此，胰岛素抵抗可能会加剧MS和胰岛素抵抗状态共有的现象，如认知障碍和炎症反应升高。有趣的是，用于治疗2型糖尿病患者的噻唑烷二酮类药物已被提议作为治疗阿尔茨海默病和MS的潜在治疗药物。这些药物可提高胰岛素敏感性，降低高胰岛素血症，并发挥抗炎作用。正在进行的研究将确定噻唑烷二酮类药物是否能改善2型糖尿病或阿尔茨海默病患者的认知功能。未来需要开展研究来检验噻唑烷二酮类药物对MS患者的影响。
